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Microbial Drug Resistance (Larchmont,... Sep 2016Cell wall recycling and β-lactam antibiotic resistance are linked in Enterobacteriaceae and in Pseudomonas aeruginosa. This process involves a large number of murolytic... (Review)
Review
Cell wall recycling and β-lactam antibiotic resistance are linked in Enterobacteriaceae and in Pseudomonas aeruginosa. This process involves a large number of murolytic enzymes, among them a cytoplasmic peptidoglycan amidase AmpD, which plays an essential role by cleaving the peptide stem from key intermediates en route to the β-lactamase production (a resistance mechanism) and cell wall recycling. Uniquely, P. aeruginosa has two additional paralogues of AmpD, designated AmpDh2 and AmpDh3, which are periplasmic enzymes. Despite the fact that AmpDh2 and AmpDh3 share a common motif for their respective catalytic domains, they are each comprised of multidomain architectures and exhibit distinct oligomerization properties. We review herein the structural and biochemical properties of orthologous and paralogous AmpD proteins and discuss their implication in cell wall recycling and antibiotic resistance processes.
Topics: Bacterial Proteins; Catalytic Domain; Cell Wall; Drug Resistance, Microbial; Enterobacteriaceae; Gene Expression; Isoenzymes; Metalloproteases; Models, Molecular; N-Acetylmuramoyl-L-alanine Amidase; Peptidoglycan; Periplasm; Protein Multimerization; Protein Structure, Secondary; Pseudomonas aeruginosa; Structural Homology, Protein; Virulence Factors
PubMed: 27326855
DOI: 10.1089/mdr.2016.0083 -
EcoSal Plus Feb 2019The type II secretion system (T2SS) delivers toxins and a range of hydrolytic enzymes, including proteases, lipases, and carbohydrate-active enzymes, to the cell surface... (Review)
Review
The type II secretion system (T2SS) delivers toxins and a range of hydrolytic enzymes, including proteases, lipases, and carbohydrate-active enzymes, to the cell surface or extracellular space of Gram-negative bacteria. Its contribution to survival of both extracellular and intracellular pathogens as well as environmental species of proteobacteria is evident. This dynamic, multicomponent machinery spans the entire cell envelope and consists of a cytoplasmic ATPase, several inner membrane proteins, a periplasmic pseudopilus, and a secretin pore embedded in the outer membrane. Despite the -envelope configuration of the T2S nanomachine, proteins to be secreted engage with the system first once they enter the periplasmic compartment via the Sec or TAT export system. Thus, the T2SS is specifically dedicated to their outer membrane translocation. The many sequence and structural similarities between the T2SS and type IV pili suggest a common origin and argue for a pilus-mediated mechanism of secretion. This minireview describes the structures, functions, and interactions of the individual T2SS components and the general architecture of the assembled T2SS machinery and briefly summarizes the transport and function of a growing list of T2SS exoproteins. Recent advances in cryo-electron microscopy, which have led to an increased understanding of the structure-function relationship of the secretin channel and the pseudopilus, are emphasized.
Topics: Adenosine Triphosphatases; Bacterial Proteins; Cryoelectron Microscopy; Fimbriae, Bacterial; Gram-Negative Bacteria; Membrane Proteins; Models, Molecular; Periplasm; Protein Binding; Secretin; Type II Secretion Systems
PubMed: 30767847
DOI: 10.1128/ecosalplus.ESP-0034-2018 -
PLoS Biology Jan 2018Gram-negative bacteria are surrounded by two membrane bilayers separated by a space termed the periplasm. The periplasm is a multipurpose compartment separate from the...
Gram-negative bacteria are surrounded by two membrane bilayers separated by a space termed the periplasm. The periplasm is a multipurpose compartment separate from the cytoplasm whose distinct reducing environment allows more efficient and diverse mechanisms of protein oxidation, folding, and quality control. The periplasm also contains structural elements and important environmental sensing modules, and it allows complex nanomachines to span the cell envelope. Recent work indicates that the size or intermembrane distance of the periplasm is controlled by periplasmic lipoproteins that anchor the outer membrane to the periplasmic peptidoglycan polymer. This periplasm intermembrane distance is critical for sensing outer membrane damage and dictates length of the flagellar periplasmic rotor, which controls motility. These exciting results resolve longstanding debates about whether the periplasmic distance has a biological function and raise the possibility that the mechanisms for maintenance of periplasmic size could be exploited for antibiotic development.
Topics: Bacterial Outer Membrane Proteins; Bacterial Proteins; Cell Membrane; Cell Wall; Cytoplasm; Gram-Negative Bacteria; Peptidoglycan; Periplasm; Spatial Analysis
PubMed: 29342145
DOI: 10.1371/journal.pbio.2004935 -
Current Opinion in Microbiology Dec 2016The Gram-positive cell envelope serves as a molecular platform for surface display of capsular polysaccharides, wall teichoic acids (WTAs), lipoteichoic acids (LTAs),... (Review)
Review
The Gram-positive cell envelope serves as a molecular platform for surface display of capsular polysaccharides, wall teichoic acids (WTAs), lipoteichoic acids (LTAs), lipoproteins, surface proteins and pili. WTAs, LTAs, and sortase-assembled pili are a few features that make the Gram-positive cell envelope distinct from the Gram-negative counterpart. Interestingly, a set of LytR-CpsA-Psr family proteins, found in all Gram-positives but limited to a minority of Gram-negative organisms, plays divergent functions, while decorating the cell envelope with glycans. Furthermore, a phylum of Gram-positive bacteria, the actinobacteria, appear to employ oxidative protein folding as the major folding mechanism, typically occurring in an oxidizing environment of the Gram-negative periplasm. These distinctive features will be highlighted, along with recent findings in the cell envelope biogenesis.
Topics: Actinobacteria; Cell Membrane; Cell Wall; Gram-Positive Bacteria; Lipopolysaccharides; Membrane Proteins; Periplasm; Polysaccharides; Protein Folding; Teichoic Acids
PubMed: 27497053
DOI: 10.1016/j.mib.2016.07.015 -
Molekuliarnaia Biologiia 2019This review summarizes the main achievements of recent years in molecular organization research of yeast cell surface, i.e., the compartment that consists of the... (Review)
Review
This review summarizes the main achievements of recent years in molecular organization research of yeast cell surface, i.e., the compartment that consists of the coordinately functioning plasma membrane, periplasmic space, and cell wall. There are data on vesicular transport to the external environment through the cell wall and the formation of channels in the wall, which indicate the possibility of dynamic rearrangements of the molecular structure of the yeast cell wall. There is an idea about the mosaic arrangement of the compartments of the plasma membrane. The hypothesis has been suggested on the heterogeneity of the molecular structure of the cell wall, which is usually considered as uniform except for the budding zones. The groups of proteins that form the molecular assembly of the yeast cell surface have been described. Special attention has been paid for proteins with amyloid properties, including Bgl2p glucanosyltransglycosylase, which is important for virulence in pathogenic yeast, and Gas1p, the first of the studied proteins of the cell surface, which is involved in the regulation of ribosomal DNA transcriptional silencing. The data on the structure of receptors localized on the cell surface and the "moonlight" proteins, involved in the cell stress response of yeasts, have been given.
Topics: Amyloid; Cell Membrane; Cell Wall; Periplasm; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 31876276
DOI: 10.1134/S0026898419060065 -
Current Issues in Molecular Biology 2018In this review we examine the use of secretion systems by bacteria to subvert host functions. Bacteria have evolved multiple systems to interact with and overcome their... (Review)
Review
In this review we examine the use of secretion systems by bacteria to subvert host functions. Bacteria have evolved multiple systems to interact with and overcome their eukaryotic host and other prokaryotes. Secretion systems are required for the release of several effectors through the bacterial membrane(s) into the extracellular space or directly into the cytoplasm of the host. We review the secretion systems of Gram-positive and Gram-negative bacteria and describe briefly the structural composition of the seven secretion systems that have been associated with increased virulence through subversion of host functions. Some of the effects of such systems on eukaryotic host processes have been studied extensively. We also describe the best-characterized effectors of each secretion system to give an overview of the molecular mechanisms employed by bacteria to hide from the immune system and convert eukaryotic cells into optimal ecological niches for their replication.
Topics: Animals; Bacterial Proteins; Bacterial Secretion Systems; Eukaryotic Cells; Gene Expression Regulation, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Host-Pathogen Interactions; Humans; Models, Molecular; Periplasm; Protein Structure, Secondary; Protein Transport; Virulence; Virulence Factors
PubMed: 28875938
DOI: 10.21775/cimb.025.001 -
FEBS Letters Jun 2015Exposure of cells to elevated levels of reactive oxygen species (ROS) damages DNA, membrane lipids and proteins, which can potentially lead to cell death. In proteins,... (Review)
Review
Exposure of cells to elevated levels of reactive oxygen species (ROS) damages DNA, membrane lipids and proteins, which can potentially lead to cell death. In proteins, the sulfur-containing residues cysteine and methionine are particularly sensitive to oxidation, forming sulfenic acids and methionine sulfoxides, respectively. The presence of protection mechanisms to scavenge ROS and repair damaged cellular components is therefore essential for cell survival. The bacterial cell envelope, which constitutes the first protection barrier from the extracellular environment, is particularly exposed to the oxidizing molecules generated by the host cells to kill invading microorganisms. Therefore, the presence of oxidative stress defense mechanisms in that compartment is crucial for cell survival. Here, we review recent findings that led to the identification of several reducing pathways protecting the cell envelope from oxidative damage. We focus in particular on the mechanisms that repair envelope proteins with oxidized cysteine and methionine residues and we discuss the major questions that remain to be solved.
Topics: Bacteria; Cell Wall; Disulfides; Oxidative Stress; Periplasm; Reactive Oxygen Species
PubMed: 25957772
DOI: 10.1016/j.febslet.2015.04.057 -
Biomolecules Jun 2023Efflux pumps are a relevant factor in antimicrobial resistance. In , the tripartite efflux pump AcrAB-TolC removes a chemically diverse set of antibiotics from the...
Efflux pumps are a relevant factor in antimicrobial resistance. In , the tripartite efflux pump AcrAB-TolC removes a chemically diverse set of antibiotics from the bacterium. Therefore, small molecules interfering with efflux pump function are considered adjuvants for improving antimicrobial therapies. Several compounds targeting the periplasmic adapter protein AcrA and the efflux pump AcrB have been identified to act synergistically with different antibiotics. Among those, several 4(3-aminocyclobutyl)pyrimidin-2-amines have been shown to bind to both proteins. In this study, we intended to identify analogs of these substances with improved binding affinity to AcrA using virtual screening followed by experimental validation. While we succeeded in identifying several compounds showing a synergistic effect with erythromycin on , biophysical studies suggested that 4(3-aminocyclobutyl)pyrimidin-2-amines form colloidal aggregates that do not bind specifically to AcrA. Therefore, these substances are not suited for further development. Our study emphasizes the importance of implementing additional control experiments to identify aggregators among bioactive compounds.
Topics: Membrane Transport Proteins; Escherichia coli; Escherichia coli Proteins; Periplasm; Anti-Bacterial Agents; Multidrug Resistance-Associated Proteins
PubMed: 37371580
DOI: 10.3390/biom13061000 -
Biochimica Et Biophysica Acta Aug 2014Outer membrane vesicles (OMVs) are constitutively produced by all Gram-negative bacteria. OMVs form when buds from the outer membrane (OM) of cells encapsulate... (Review)
Review
Outer membrane vesicles (OMVs) are constitutively produced by all Gram-negative bacteria. OMVs form when buds from the outer membrane (OM) of cells encapsulate periplasmic material and pinch off from the OM to form spheroid particles approximately 10 to 300nm in diameter. OMVs accomplish a diversity of functional roles yet the OMV's utility is ultimately determined by its unique composition. Inclusion into OMVs may impart a variety of benefits to the protein cargo, including: protection from proteolytic degradation, enhancement of long-distance delivery, specificity in host-cell targeting, modulation of the immune response, coordinated secretion with other bacterial effectors, and/or exposure to a unique function-promoting environment. Many enriched OMV-associated components are virulence factors, aiding in host cell destruction, immune system evasion, host cell invasion, or antibiotic resistance. Although the mechanistic details of how proteins become enriched as OMV cargo remain elusive, recent data on OM biogenesis and relationships between LPS structure and OMV-cargo inclusion rates shed light on potential models for OM organization and consequent OMV budding. In this review, mechanisms based on pre-existing OM microdomains are proposed to explain how cargo may experience differing levels of enrichment in OMVs and degrees of association with OMVs during extracellular export. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.
Topics: Bacterial Outer Membrane Proteins; Gram-Negative Bacteria; Periplasm; Periplasmic Proteins; Protein Transport; Transport Vesicles; Virulence Factors
PubMed: 24370777
DOI: 10.1016/j.bbamcr.2013.12.011 -
The Journal of Biological Chemistry Mar 2022Understanding the evolution of metallo-β-lactamases (MBLs) is fundamental to deciphering the mechanistic basis of resistance to carbapenems in pathogenic and... (Review)
Review
Understanding the evolution of metallo-β-lactamases (MBLs) is fundamental to deciphering the mechanistic basis of resistance to carbapenems in pathogenic and opportunistic bacteria. Presently, these MBL-producing pathogens are linked to high rates of morbidity and mortality worldwide. However, the study of the biochemical and biophysical features of MBLs in vitro provides an incomplete picture of their evolutionary potential, since this limited and artificial environment disregards the physiological context where evolution and selection take place. Herein, we describe recent efforts aimed to address the evolutionary traits acquired by different clinical variants of MBLs in conditions mimicking their native environment (the bacterial periplasm) and considering whether they are soluble or membrane-bound proteins. This includes addressing the metal content of MBLs within the cell under zinc starvation conditions and the context provided by different bacterial hosts that result in particular resistance phenotypes. Our analysis highlights recent progress bridging the gap between in vitro and in-cell studies.
Topics: Anti-Bacterial Agents; Bacteria; Carbapenems; Periplasm; beta-Lactamases
PubMed: 35120928
DOI: 10.1016/j.jbc.2022.101665